Nocturnal hypoxemic burden in patients with heart failure: Emerging prognostic role of its nonspecific component.

BACKGROUND: Nocturnal hypoxemic burden has been shown to be a robust, independent predictor of all-cause mortality in patients with heart failure and reduced ejection fraction (HFrEF) and to occur in a severe form even in patients with low or negligible frequency of respiratory events (apneas/hypopneas). This suggests the existence of two components of hypoxemic burden: one unrelated to respiratory events and the other related. The aim of this study was to characterize these two components and to evaluate their prognostic value. METHODS: Nocturnal hypoxemic burden was assessed in a cohort of 280 patients with HFrEF by measuring the percentage of sleep with an oxygen saturation (SpO2) <90% (T90), and the area of the SpO2 curve below 90% (Area90). Both indices were also recalculated within the sleep segments associated with respiratory events (event-related component: T90Eve, Area90Eve) and outside these segments (nonspecific component: T90Nspec, Area90Nspec). The outcome of the survival analysis (Cox regression) was all-cause mortality. RESULTS: During a median follow-up of 60 months, 87 patients died. T90, Area90, and their components were significant in univariate analysis (P < .05 all). However, when these indices were adjusted for known risk factors, T90, T90Nspec, Area90, and Area90Nspec remained statistically significant (P = .018, hazard ratio (HR)=1.12, 95%CI=(1.02, 1.23); P = .007, HR=1.20, 95% CI = [1.05, 1.37]; P = .020, HR = 1.05, 95% CI = [1.01, 1.10]; P = .0006, HR = 1.15, 95% CI = [1.06, 1.25]), whereas T90Eve and Area90Eve did not (P = .27, P = .28). These results were internally validated using bootstrap resampling. CONCLUSIONS: By demonstrating a significant independent association of nonspecific hypoxemic burden with all-cause mortality, this study suggests that this component of total nocturnal hypoxemic burden may play an important prognostic role in patients with HFrEF.

Impact of optimized transcutaneous auricular vagus nerve stimulation on cardiac autonomic profile in healthy subjects and heart failure patients.

Objective.To determine the optimal frequency and site of stimulation for transcutaneous vagus nerve stimulation (tVNS) to induce acute changes in the autonomic profile (heart rate (HR), heart rate variability (HRV)) in healthy subjects (HS) and patients with heart failure (HF).Approach.We designed three single-blind, randomized, cross-over studies: (1) to compare the acute effect of left tVNS at 25 Hz and 10 Hz (n= 29, age 60 ± 7 years), (2) to compare the acute effect of left and right tVNS at the best frequency identified in study 1 (n= 28 age 61 ± 7 years), and (3) to compare the acute effect of the identified optimal stimulation protocol with sham stimulation in HS and HF patients (n= 30, age 59 ± 5 years, andn= 32, age 63 ± 7 years, respectively).Main results.In study 1, left tragus stimulation at 25 Hz was more effective than stimulation at 10 Hz in decreasing HR (-1.0 ± 1.2 bpm,p< 0.001 and -0.5 ± 1.6 bpm, respectively) and inducing vagal effects (significant increase in RMSSD, and HF power). In study 2, the HR reduction was greater with left than right tragus stimulation (-0.9 ± 1.5 bpm,p< 0.01 and -0.3 ± 1.4 bpm, respectively). In study 3 in HS, left tVNS at 25 Hz significantly reduced HR, whereas sham stimulation did not (-1.1 ± 1.2 bpm,p< 0.01 and -0.2 ± 2.9 bpm, respectively). In HF patients, both active and sham stimulation produced negligible effects.Significance.Left tVNS at 25 Hz is effective in acute modulation of cardiovascular autonomic control (HR, HRV) in HS but not in HF patients (NCT05789147).

Effect of lateral position on rostral fluid shift and relationship to severity of Cheyne-Stokes respiration in heart failure patients.

PURPOSE: Lateral sleep position has a significant beneficial effect on the severity of Cheyne-Stokes respiration with central sleep apnea (CSR-CSA) in patients with heart failure (HF). We hypothesized that a reduction in rostral fluid shift from the legs in this position compared with the supine position may contribute to this effect. METHODS: In patients with CSR-CSA and an apnea-hypopnea index (AHI) ≥ 15/h (by standard polysomnography), uncalibrated leg fluid volume was measured in the supine, left lateral decubitus, and right lateral decubitus positions (in-laboratory assessment). The correlation between postural changes in fluid volume and corresponding changes in AHI was evaluated. Since there was no difference in both leg fluid volume and AHI between the right and left positions, measurements in these two conditions were combined into a single lateral position. RESULTS: In 18 patients with CSR-CSA, leg fluid volume increased by 2.7 ± 3.1% (p = 0.002) in the lateral position compared to the supine position, while AHI decreased by 46 ± 20% (p < 0.0001) with the same postural change. The correlation between postural changes in AHI and leg fluid volume was 0.22 (p = 0.42). Changes in leg fluid volume were a slow phenomenon, whereas changes in CSR-CSA severity were almost synchronous with changes in posture. CONCLUSION: Lateral position causes a reduction in rostral fluid shift compared to the supine position, but this change does not correlate with the corresponding change in CSR-CSA severity. The two changes occur on different time scales. These findings question the role of postural changes in rostral fluid shift as a determinant of corresponding changes in CSR-CSA severity.

Postural changes in lung volumes in patients with heart failure and Cheyne-Stokes respiration: Relationship with sleep apnea severity.

BACKGROUND AND AIM: It has been proposed that the increased severity of sleep apnea frequently observed in heart failure (HF) patients with Cheyne-Stokes respiration (CSR) when sleeping in the supine compared to the lateral position, may be caused by the concomitant reduction in functional residual capacity (FRC). We assessed positional changes in FRC in patients with CSR and investigated the relationship between these changes in the laboratory and corresponding changes in CSR severity during sleep. METHODS: After a diagnostic polysomnography, 18 HF patients with dominant CSR and an apnea-hypopnea index (AHI)≥15 events/h underwent a standard pulmonary function test in the sitting position. Measurements were repeated in the supine, left lateral and right lateral. The latter two measurements were averaged to obtain a single lateral measurement. RESULTS: The FRC in the seated position was 3.0 ± 0.5 L (85 ± 13% of predicted), decreased to 2.3 ± 0.3 L (-21 ± 8%, p < 0.0001) in the supine position, and increased to 2.8 ± 0.4 L (+21 ± 12%, p < 0.0001) from the supine to the lateral position (-5±8% vs seated, p = 0.013). During sleep, the AHI and the apnea index (AI) decreased from 47 ± 15 events/h to 26 ± 12 events/h (-46 ± 20%, p < 0.0001) and from 29 ± 21 events/h to 12 ± 10 events/h (-61 ± 40%, p < 0.001) from the supine to the lateral position. Changes in the AI were significantly correlated with corresponding changes in FRC (ρ = -0.55, p = 0.032). CONCLUSION: In patients with HF and CSR, lying in the supine position causes a significant reduction in FRC in the context of a chronically reduced FRC. The negative correlation between postural changes in FRC and AI supports the hypothesis that the reduction in lung gas stores in the supine position may promote/exacerbate respiratory control instability.

Effect of Algorithmic Music Listening on Cardiac Autonomic Nervous System Activity: An Exploratory, Randomized Crossover Study.

It is proven that music listening can have a therapeutic impact in many clinical fields. However, to assume a curative value, musical stimuli should have a therapeutic logic. This study aimed at assessing short-term effects of algorithmic music on cardiac autonomic nervous system activity. Twenty-two healthy subjects underwent a crossover study including random listening to relaxing and activating algorithmic music. Electrocardiogram (ECG) and non-invasive arterial blood pressure were continuously recorded and were later analyzed to measure Heart Rate (HR) mean, HR variability and baroreflex sensitivity (BRS). Statistical analysis was performed using a general linear model, testing for carryover, period and treatment effects. Relaxing tracks decreased HR and increased root mean square of successive squared differences of normal-to-normal (NN) intervals, proportion of interval differences of successive NN intervals greater than 50 ms, low-frequency (LF) and high-frequency (HF) power and BRS. Activating tracks caused almost no change or an opposite effect in the same variables. The difference between the effects of the two stimuli was statistically significant in all these variables. No difference was found in the standard deviation of normal-to-normal RR intervals, LFpower in normalized units and LFpower/HFpower variables. The study suggests that algorithmic relaxing music increases cardiac vagal modulation and tone. These results open interesting perspectives in various clinical areas.

Computer-Assisted Assessment of the Interaction Between Arousals, Breath-by-Breath Ventilation, and Chemical Drive During Cheyne-Stokes Respiration in Heart Failure Patients.

Transient increases in ventilation induced by arousal from sleep during Cheyne-Stokes respiration in heart failure patients are thought to contribute to sustaining and exacerbating the ventilatory oscillation. The only possibility to investigate the validity of this notion is to use observational data. This entails some significant challenges: (i) accurate identification of both arousal onset and offset; (ii) detection of short arousals (<3 s); (iii) breath-by-breath analysis of the interaction between arousals and ventilation; (iv) careful control for important confounding factors. In this paper we report how we have tackled these challenges by developing innovative computer-assisted methodologies. The identification of arousal onset and offset is performed by a hybrid approach that integrates visual scoring with computer-based automated analysis. We use a statistical detector to automatically discriminate between dominant theta-delta and dominant alpha activity at each instant of time. Moreover, a statistical detector is used to validate visual scoring of K complexes, delta waves or artifacts associated with an EEG frequency shift, as well as frequency shifts to beta activity. A high-resolution (250 ms) state-transition diagram providing continuous information on the sleep-wake state of the subject is finally obtained. Based on this information, arousals are automatically identified as any state change from sleep to wakefulness lasting ≥2 s. The assessment of the interaction between arousals and ventilation is performed using a breath-by-breath, case-control approach. The arousal-associated change in ventilation is measured as the normalized difference between minute ventilation in the case breath (i.e., with arousal) and that in the control breath (i.e., without arousal), controlling for sleep stage and chemical drive. The latter is estimated by using information from pulse oximetry at the finger. In the last part of the paper, we discuss main potential sources of error inherent in the described methodologies.

Baroreceptor Sensitivity in Individuals with CKD and Heart Failure.

Background: Heart failure is the most common cardiovascular complication of chronic kidney disease (CKD) and foreshadows a high morbidity and mortality rate. Baroreflex impairment likely contributes to cardiovascular mortality. We aimed to study the associations between CKD, heart failure, and baroreflex sensitivity (BRS) and their association with cardiovascular outcomes. Methods: We retrospectively analyzed data from a cohort of 247 individuals with moderate to severe HF. All subjects underwent BRS measurements after intravenous phenylephrine along with electrocardiography, echocardiography, and laboratory measurements. We used logistic regression models to assess the association of CKD (estimated glomerular filtration rate <60 ml/min per 1.73 m2) with BRS using iterative models. Cox proportional hazards models were used to assess associations of binary BRS and subgroups according to categorizations of CKD and BRS with cardiovascular mortality. Results: Median eGFR among individuals with CKD was 52 (IQR 44-56) ml/min per 1.73 m2. eGFR was lower in those with depressed BRS (65 [IQR 54-76] ml/min per 1.73 m2) compared with those with preserved BRS (73 [IQR 64-87] ml/min per 1.73 m2; P≤0.001). The majority of individuals with CKD had depressed BRS compared with those without CKD (60% versus 29%; P=0.05). In regression models, CKD and BRS were independently associated. Cardiovascular mortality was significantly increased in individuals with or without CKD and depressed BRS compared with those with preserved BRS and CKD. Conclusions: Cardiac BRS is depressed in patients with mild to moderate CKD and HF and associated with cardiovascular mortality. Additional study to confirm its contribution to cardiovascular mortality, particularly in advanced CKD, is warranted.

Determinants of Sleepiness at Wheel and Missing Accidents in Patients With Obstructive Sleep Apnea.

STUDY OBJECTIVES: Motor-vehicle crashes are frequent in untreated OSA patients but there is still uncertainty on prevalence as well as physiological or clinical determinants of sleepiness at the wheel (SW) in OSA patients. We assessed determinants of SW or sleepiness related near-miss car accident (NMA) in a group of non-professional drivers with OSA. METHODS: A 237 consecutive, treatment-naïve PSG-diagnosed OSA patients (161 males, 53.1 ± 12.6 years) were enrolled. Self-reported SW was assessed by positive answer to the question, "Have you had episodes of falling asleep while driving or episodes of drowsiness at wheel that could interfere with your driving skill in the last year?" Occurrence of NMA in the last 3 years was also individually recorded. Habitual self-reported average sleep time was collected. RESULTS: SW was found in 41.3% of patients but one-quarter of patients with SW did not report excessive daytime sleepiness. Predictors of SW were the following subjective factors: Epworth sleepiness scale score (ESS-OR 1.26; IC 1.1-1.4; p < 0.0001), depressive symptoms (BDI-OR 1.2; IC 1.06-1.18; p < 0.0001) and level of risk exposure (annual mileage-OR 1.9; IC 1.15-3.1; p = 0.007). NMAs were reported by 9.7% of patients, but more frequently by SW+ than SW- (22.4% vs. 0.7%; χ2 31, p < 0.0001). The occurrence of NMAs was significantly associated to ESS, BDI, habitual sleep duration and ODI (R 2 = 0.41). CONCLUSION: SW is not predicted by severity of OSA. Evaluation of risk exposure, assessment of depressive symptoms, and reported NMA should be included in the clinical evaluation, particularly in patients with reduced habitual sleep time and severe nocturnal hypoxia.

Lack of association between heart period variability asymmetry and respiratory sinus arrhythmia in healthy and chronic heart failure individuals.

Temporal asymmetry is a peculiar aspect of heart period (HP) variability (HPV). HPV asymmetry (HPVA) is reduced with aging and pathology, but its origin is not fully elucidated. Given the impact of respiration on HPV resulting in the respiratory sinus arrhythmia (RSA) and the asymmetric shape of the respiratory pattern, a possible link between HPVA and RSA might be expected. In this study we tested the hypothesis that HPVA is significantly associated with RSA and asymmetry of the respiratory rhythm. We studied 42 middle-aged healthy (H) subjects, and 56 chronic heart failure (CHF) patients of whom 26 assigned to the New York Heart Association (NYHA) class II (CHF-II) and 30 to NYHA class III (CHF-III). Electrocardiogram and lung volume were monitored for 8 minutes during spontaneous breathing (SB) and controlled breathing (CB) at 15 breaths/minute. The ratio of inspiratory (INSP) to expiratory (EXP) phases, namely the I/E ratio, and RSA were calculated. HPVA was estimated as the percentage of negative HP variations, traditionally measured via the Porta's index (PI). Departures of PI from 50% indicated HPVA and its significance was tested via surrogate data. We found that RSA increased during CB and I/E ratio was smaller than 1 in all groups and experimental conditions. In H subjects the PI was about 50% during SB and it increased significantly during CB. In both CHF-II and CHF-III groups the PI was about 50% during SB and remained unmodified during CB. The PI was uncorrelated with RSA and I/E ratio regardless of the experimental condition and group. Pooling together data of different experimental conditions did not affect conclusions. Therefore, we conclude that the HPVA cannot be explained by RSA and/or I/E ratio, thus representing a peculiar feature of the cardiac control that can be aroused in middle-aged H individuals via CB.

Interaction Between Arousals and Ventilation During Cheyne-Stokes Respiration in Heart Failure Patients: Insights From Breath-by-Breath Analysis.

Study Objectives: Arousals from sleep during the hyperpneic phases of Cheyne-Stokes respiration with central sleep apnea (CSR-CSA) in patients with heart failure are thought to cause ventilatory overshoot and a consequent longer apnea, thereby sustaining and exacerbating ventilatory instability. However, data supporting this model are lacking. We investigated the relationship between arousals, hyperpnea and post-hyperpnea apnea length during CSR-CSA. Methods: Breath-by-breath changes in ventilation associated with the occurrence of arousal were evaluated in 18 heart failure patients with CSR-CSA, apnea-hypopnea index ≥15/h and central apnea index ≥5/h. The change in apnea length associated with the presence of arousal during the previous hyperpnea was also evaluated. Potential confounding variables (chemical drive, sleep stage) were controlled for. Results: Arousals were associated with a large increase in ventilation at the beginning of the hyperpnea (+76 ± 35%, p < 0.0001), that rapidly declined during its crescendo phase. Around peak hyperpnea, the change in ventilation was -8 ± 26% (p = 0.14). The presence of arousal during the hyperpnea was associated with a median increase in the length of the subsequent apnea of +4.6% (Q1, Q2: -0.7%, 20.5%; range: -8.5%, 36.2%) (p = 0.021). The incidence of arousals occurring at the beginning of hyperpnea and mean ventilation in the region around its peak were independent predictors of the change in apnea length (p = 0.004 and p = 0.015, respectively; R2 = 0.78). Conclusions: Arousals from sleep during CSR-CSA in heart failure patients are associated with a rapidly decreasing ventilatory overshoot at the beginning of the hyperpnea, followed by a tendency toward a slight ventilatory undershoot around its peak. On average, arousals are also associated with a modest increase in post-hyperpnea apnea length; however, large increases in apnea length (>20%) occur in about a quarter of the patients.

CARDIAC chronotropic effects of sleep-disordered breathing in patients with heart failure.

It is still not known whether the oscillation in heart rate (HR) induced by sleep-disordered breathing (SDB) in patients with heart failure entails significant chronotropic effects. We hypothesised that since cyclical changes in ventilation and arterial blood gases during SDB affect HR through multiple and complexly interacting mechanisms characterised by large inter-subject variability, chronotropic effects may change from patient to patient. A total of 42 patients with moderate-to-severe chronic heart failure with systolic dysfunction underwent an in-hospital sleep study. Chronotropic effects of SDB were quantified by comparing the distribution of instantaneous HR during SDB with that during periods without SDB (noSDB) within the same night in each patient. Based on distribution changes from noSDB to SDB, 12, nine, 11, and 10 patients showed a significant tachycardic, bradycardic, tachycardic and bradycardic, and neither significant tachycardic nor significant bradycardic effect, respectively. Tachycardic and bradycardic effects were primarily due to an increase in the rate rather than in the magnitude of cyclical HR elevations and reductions, and were more prevalent and severe in patients with dominant obstructive and central events, respectively. The apnea-hypopnea index did not differ between groups. Conversely, the time spent with an oxygen saturation of <90% was greater in the tachycardic and tachycardic-bradycardic groups compared to the bradycardic group. These findings indicate that HR distribution changes induced by SDB can vary from patient to patient revealing four distinct and well-characterised chronotropic effects. These effects are related to the degree of hypoxic burden brought about by SDB and are affected by the type of sleep apnea (central/obstructive).

Upper Limb Interactive Weightless Technology-Aided Intervention and Assessment Picks Out Motor Skills Improvement in Parkinson's Disease: A Pilot Study.

Background: In Parkinson's disease, reaching movements are conditioned by motor planning and execution deficiency. Recently, rehabilitation, aided by high technological devices, was employed for Parkinson's disease. Objective: We aimed to (1) investigate the changes in the upper limb motor performances in a sample of a patient with Parkinson's disease after a weightless training, with a passive exoskeleton, in an augmented-feedback environment; (2) highlight differences by motor parameters (performance, speed, and movement accuracy) and by type of movement (simple or complex); and (3) evaluate movement improvements by UPDRS II-III. Methods: Observational pilot study. Twenty right-handed patients with Parkinson's disease, Hohen and Yahr 2, Mini Mental State Examination ≥24 were evaluated. All patients underwent 5 day/week sessions for 4 weeks, 30 min for each arm; the training was performed with 12 exercises (single and multi-joints, horizontal and vertical movements). All the patients were assessed by UPDRS II-III and the evaluation tests provided by the device's software: a simple movement, the vertical capture, and a complex movement, the horizontal capture. For each test, we analyzed reached target percentage, movement execution time, and accuracy. Results: After training, a significant improvement of accuracy and speed for simple movement on the dominant arm, of reached targets and speed for complex movement on both sides were shown. UPDRS II and III improved significantly after training. Conclusions: In our study, a motor training aided by a high technological device improves motor parameters and highlights differences between the type of movement (simple or complex) and movement parameters (speed and accuracy) in a sample of patients with Parkinson's disease.

Quantitative assessment of the quality of home sleep studies: A computer-assisted approach.

Home monitoring is the most practical means of collecting sleep data in large-scale research investigations. Because the portion of recording time with poor-quality data is higher than in attended polysomnography, a quantitative assessment of the quality of each signal should be recommended. Currently, only qualitative or semi-quantitative assessments are carried out, likely because of the lack of computer-based applications to carry out this task efficiently. This paper presents an innovative computer-assisted procedure designed to perform a quantitative quality assessment of standard respiratory signals recorded by Type 2 and Type 3 portable sleep monitors. The proposed system allows to assess the quality (good versus bad) of consecutive 1-min segments of thoraco-abdominal movements, oronasal, nasal airflow and oxygen saturation through an automatic classifier. The performance of the classifier was evaluated in a sample of 30 unattended polysomnography recordings, comparing the computer output with the consensus of two expert scorers. The difference (computer versus scorers) in the percentage of good-quality segments was on average very small, ranging from -3.1% (abdominal movements) to 0.8% (nasal flow), with an average total classification accuracy from 90.2 (oronasal flow) to 94.9 (nasal flow), a Sensitivity from 0.93 (oronasal flow) to 0.98 (nasal flow), and a Specificity from 0.74 (nasal flow) to 0.86 (abdominal movements). In practical applications, the scorer can run a check-and-edit procedure, further improving the classification accuracy. Considering a sample of 270 unattended polysomnography recordings (recording time: 545 ± 44 min), the average time taken for the check-and-edit procedure of each recording was 6.9 ± 2.1 min for all respiratory signals.

Cardiac and Peripheral Autonomic Responses to Orthostatic Stress During Transcutaneous Vagus Nerve Stimulation in Healthy Subjects.

Previous studies showed that transcutaneous vagus nerve stimulation (tVNS) modulates the autonomic nervous system (ANS) in resting condition. However, the autonomic regulation in response to an orthostatic challenge during tVNS in healthy subjects remains unknown. We tested the hypothesis that tVNS reduces heart rate (HR) and alters the responsivity of ANS to orthostatic stress in healthy subjects. In a randomized and cross-over trial, thirteen healthy subjects underwent two experimental sessions on different days: (1) tVNS and (2) control. Using a tVNS device, an auricular electrode was placed on the left cymba conchae of the external ear; an electric current with a pulse frequency of 25 Hz and amplitude between 1 and 6 mA was applied. For the assessment of ANS, the beat-to-beat HR and systolic arterial pressure (SAP) were analyzed using linear and nonlinear approaches during clinostatic and orthostatic conditions. In clinostatic conditions, tVNS reduced HR (p < 0.01), SAP variability (p < 0.01), and cardiac and peripheral sympathetic modulation (p < 0.01). The responsivity of the peripheral sympathetic modulation to orthostatic stress during tVNS was significantly higher when compared to the control session (p = 0.03). In conclusion, tVNS reduces the HR and affects cardiac and peripheral autonomic control and increases the responses of peripheral autonomic control to orthostatic stress in healthy subjects.

Arterial oxygen saturation during Cheyne-Stokes respiration in heart failure patients: does measurement site matter?

OBJECTIVE: Despite the fact that the ear is the site to monitor arterial oxygen saturation by pulse oximetry (SpO2) closest to carotid chemoreceptors, sleep studies almost invariably use finger probes. This study aimed to assess the timing and morphological differences between SpO2 signals at the ear and finger during Cheyne-Stokes respiration (CSR) in heart failure (HF) patients. METHODS: We studied 21 HF patients with CSR during a 40-min in-laboratory resting recording. SpO2 was recorded by: (1) two identical bedside pulse-oximeters with an ear (SpO2_Ear) and a finger probe (SpO2_Finger), and (2) a standard polysomnograph with a finger probe (SpO2_PSG). We estimated the delays between signals and, for each signal, computed the mean and minimum SpO2, the magnitude of cyclic desaturations and the overall time spent with SpO2<90% (T90%). RESULTS: The SpO2_Finger signal was significantly delayed [bias: 12.7 s (95% limits of agreement: 2.2, 23.0 s)] and slightly but not significantly downward-shifted with respect to SpO2_Ear. SpO2_PSG was almost synchronous with SpO2_Finger; however, a further significant downward shift was observed relative to the latter. In particular, minimum SpO2_PSG was significantly lower [-2.1% (- 4.8, 0.6%)], and desaturations and T90% were significantly higher than SpO2_Finger [1.2% (-1.3, 3.7%), and 13.9% (-12.3, 40.0%), respectively]. CONCLUSION: During CSR in HF patients, the marked delay between SpO2_Ear and SpO2_Finger makes the interpretation of the timing relationship between peripheral chemoreceptor stimulation and ventilatory events rather difficult. The observed discrepancies between SpO2_PSG and SpO2_Finger, which may be due to differences in the processing of raw SpO2 signals, call for a standardization of processing algorithms.

Physiological and clinical characteristics of patients with COPD admitted to an inpatient pulmonary rehabilitation program: A real-life study.

BACKGROUND AND OBJECTIVE: Patient selection criteria and experimental interventions of randomized controlled trials may not reflect how things work in practice. The aim of this study was to describe the characteristics of chronic obstructive pulmonary disease (COPD) patients undergoing an inpatient pulmonary rehabilitation program (PRP) and the correlates of success. METHODS: Retrospective database review of 975 consecutive patients transferred from acute care hospitals after an acute exacerbation (group A: 14.6%) or admitted from home (group B: 75.4%), from 2010 to 2017. Patients were also divided according to the associated registered main diagnosis: COPD (group 1: 30.6%); COPD and respiratory failure (group 2: 51.7%); COPD and obstructive sleep apnea (group 3: 17.6%). Baseline correlates of post-PRP changes in six minute walking test (6MWT) were also evaluated. RESULTS: Global Initiative for Chronic Obstructive Lung Disease stages 3 and 4 were the most commonly represented in group 2 (p=0.0001). Comorbidity Index of all patients was 3.9±1.8. The overall in-hospital mortality rate was 1.3% (5.6% vs 0.6%, in groups A and B, respectively; p=0.0001). Hypertension, cardiac diseases and obesity were observed in 65.2, 52.2 and 29.6% of patients, respectively. Post-PRP 6MWT increased in all groups. Age, male gender, airway obstruction and baseline 6MWT were correlated with a post-PRP 30 meter increase in 6MWT. CONCLUSION: Confirming data of literature, this real-life study shows the characteristics of COPD patients undergoing an inpatient PRP with significant improvement in exercise capacity, independent of whether in stable state or after a recent exacerbation or of the associated main diagnosis.

Exercise Training After Pulmonary Endarterectomy for Patients with Chronic Thromboembolic Pulmonary Hypertension.

BACKGROUND: After undergoing a procedure of pulmonary endarterectomy (PEA), patients with chronic thromboembolic pulmonary hypertension (CTEPH) may still experience reduced exercise capacity. Data on effects of exercise training in these patients are scant. OBJECTIVES: To evaluate the effectiveness of exercise training after PEA for CTEPH and if the presence of "residual pulmonary hypertension" may affect the outcome. METHODS: Retrospective data analysis of CTEPH patients undergoing inpatient exercise training after PEA. According to predefined criteria, patients were divided into those with (group 1) and without (group 2) a "good" post-surgery hemodynamic response. Assessments of the 6-min walking distance test (6-min walking distance test [6 MWT]: primary outcome) were performed before and after surgery (before training), after training and at 3-month follow-up. Hemodynamic and lung function data were also analyzed. RESULTS: Data of 84 and 26 patients of groups 1 and 2, respectively, were analyzed. After surgery patients showed a reduction in 6 MWT, which significantly reversed after training and further improved at 3 months (p = 0.0001), without any significant difference between groups. The percentage of patients reaching the minimal clinically important difference in 6 MWT was similar between groups. The sig-nificant (p = 0.0001) post-surgery improvement in hemodynamics was maintained at 3 months without any significant difference between groups. New York Heart Association functional class improved in parallel to the hemodynamic improvement. CONCLUSIONS: Exercise training in patients with CTEPH after PEA, an inpatient exercise training program, improves exercise capacity for up to 3 months, independently of the post-surgery hemodynamic response.

Temporal relationship between arousals and Cheyne-Stokes respiration with central sleep apnea in heart failure patients.

OBJECTIVE: The interplay between arousals and respiratory events during Cheyne-Stokes respiration (CSR) with central sleep apnea (CSA) in heart failure (HF) patients is still not fully understood. We investigated the temporal relationship between arousals and CSR-CSA. METHODS: Episodes of CSR-CSA during sleep stages N1-N2 were analyzed in 22 HF patients with an apnea-hypopnea index ≥15/h, dominant CSA and central apnea index ≥5/h. For each CSR-CSA cycle (apnea + hyperpnea), we determined the onset (ARonset, relative to hyperpnea onset) and duration of detected arousals. RESULTS: Arousals (N = 2348) mostly occurred within the first half of the hyperpneic phase (42.6%, ARonset = 10.6 ±â€¯2.1 s; duration = 10.6 ±â€¯5.2 s) or close to hyperpnea onset (21.5%, ARonset = -0.1 ±â€¯0.6 s; duration = 13.9 ±â€¯5.4 s). Within-apnea arousals were less frequent (12.4%, ARonset = -16.0 ±â€¯4.7 s; duration = 3.8 ±â€¯1.4 s). The proportion of CSR-CSA cycles without any hyperpnea-related arousal was 27.5 ±â€¯18.2%. Hyperpnea-related arousability (total number of hyperpneic arousals/total duration of hyperpneas) and apnea-related arousability were 63.4 ±â€¯21.0/h and 23.8 ±â€¯16.9/h, respectively (p < 0.0001). CONCLUSION: During CSR-CSA, a significant proportion of arousals occur at hyperpnea onset, indicating a low arousal threshold. Hyperpneic arousals are not essential for CSR-CSA. Arousability markedly increases during hyperpneas, likely due to the concurrent increase in chemoreceptor stimulation. SIGNIFICANCE: This study extends current knowledge on the interplay between sleep instability and respiratory events during CSR-CSA.

Chronic thromboembolic pulmonary hypertension: Reversal of pulmonary hypertension but not sleep disordered breathing following pulmonary endarterectomy.

BACKGROUND: It has been hypothesized that pre-capillary pulmonary hypertension (PH) may trigger sleep disordered breathing (SDB). In patients with chronic thromboembolic PH (CTEPH), pulmonary endarterectomy (PEA) is potentially effective to improve PH. We assessed the pre- and post-operative prevalence of SDB in CTEPH patients submitted to PEA and the relationship between SDB and clinical, pulmonary and hemodynamic factors. METHODS: Unattended cardiorespiratory recording was performed the night before and one month after elective PEA in 50 patients. RESULTS: Before the intervention SDB prevalence (obstructive or central AHI ≥ 5/h) was 64%: 18 patients (66% female) had No-SDB, 22 (68% female) had dominant obstructive (dOSA), and 10 (20% female) had dominant central sleep apnea (dCSA). There were no differences in risk factors and the need for supplemental oxygen. Mean right atrial (mRAP) and pulmonary artery pressures (mPAP) showed a more compromised profile from No-SDB to dOSA and dCSA (mRAP: 5.5 ±â€¯3.9 vs 7.0 ±â€¯4.5 vs 9.7 ±â€¯4.3 mm Hg (p = 0.054), mPAP: 39 ±â€¯12 vs 48 ±â€¯11 vs 51 ±â€¯16 mm Hg (p = 0.0.47)). By contrast, cardiac index did not differ. At post-intervention, the prevalence of SDB was 68%: 16 patients had No-SDB, while 30 had dOSA and 4 dCSA, with no relationship with the relief from PH. Interestingly, 5 patients with previous CSA moved to the OSA group and 2 normalized. CONCLUSIONS: Prevalence of SDB is high in patients with CTEPH even after resolution of PH. Our data support the hypothesis that pre-capillary PH may trigger CSA but not OSA, and suggest that OSA may play a role in the development of CTEPH.

Paced Breathing Increases the Redundancy of Cardiorespiratory Control in Healthy Individuals and Chronic Heart Failure Patients.

Synergy and redundancy are concepts that suggest, respectively, adaptability and fault tolerance of systems with complex behavior. This study computes redundancy/synergy in bivariate systems formed by a target X and a driver Y according to the predictive information decomposition approach and partial information decomposition framework based on the minimal mutual information principle. The two approaches assess the redundancy/synergy of past of X and Y in reducing the uncertainty of the current state of X. The methods were applied to evaluate the interactions between heart and respiration in healthy young subjects (n = 19) during controlled breathing at 10, 15 and 20 breaths/minute and in two groups of chronic heart failure patients during paced respiration at 6 (n = 9) and 15 (n = 20) breaths/minutes from spontaneous beat-to-beat fluctuations of heart period and respiratory signal. Both methods suggested that slowing respiratory rate below the spontaneous frequency increases redundancy of cardiorespiratory control in both healthy and pathological groups, thus possibly improving fault tolerance of the cardiorespiratory control. The two methods provide markers complementary to respiratory sinus arrhythmia and the strength of the linear coupling between heart period variability and respiration in describing the physiology of the cardiorespiratory reflex suitable to be exploited in various pathophysiological settings.